Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus

Ian A. Durie, Zahra R. Tehrani, Elif Karaaslan, Teresa E. Sorvillo, Jack McGuire, Joseph W. Golden, Stephen R. Welch, Markus H. Kainulainen, Jessica R. Harmon, Jarrod J. Mousa, David Gonzalez, Suzanne Enos, Iftihar Koksal, Gurdal Yilmaz, Hanife Nur Karakoc, Sanaz Hamidi, Cansu Albay, Jessica R. Spengler, Christina F. Spiropoulou, Aura R. Garrison, Mohammad M. Sajadi, Éric Bergeron () and Scott D. Pegan ()
Additional contact information
Ian A. Durie: University of Georgia
Zahra R. Tehrani: University of Maryland School of Medicine
Elif Karaaslan: Centers for Disease Control and Prevention
Teresa E. Sorvillo: Centers for Disease Control and Prevention
Jack McGuire: University of California Riverside
Joseph W. Golden: United States Army Medical Research Institute of Infectious Diseases
Stephen R. Welch: Centers for Disease Control and Prevention
Markus H. Kainulainen: Centers for Disease Control and Prevention
Jessica R. Harmon: Centers for Disease Control and Prevention
Jarrod J. Mousa: University of Georgia College of Veterinary Medicine
David Gonzalez: University of California Riverside
Suzanne Enos: University of Georgia
Iftihar Koksal: Acibadem University Atakent Hospital
Gurdal Yilmaz: Karadeniz Technical University School of Medicine
Hanife Nur Karakoc: Bitlis State Hospital
Sanaz Hamidi: Karadeniz Technical University School of Medicine
Cansu Albay: Karadeniz Technical University School of Medicine
Jessica R. Spengler: Centers for Disease Control and Prevention
Christina F. Spiropoulou: Centers for Disease Control and Prevention
Aura R. Garrison: United States Army Medical Research Institute of Infectious Diseases
Mohammad M. Sajadi: University of Maryland School of Medicine
Éric Bergeron: University of Georgia
Scott D. Pegan: University of California Riverside

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.

Date: 2022
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DOI: 10.1038/s41467-022-34923-0

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